title: Imaging and cerebrospinal fluid biomarkers in the search for Alzheimer's disease mechanisms.
abstract: BACKGROUND
  The pathophysiological process of Alzheimer's disease (AD) begins many years before the emergence of clinical symptoms (preclinical AD). A hypothetical biomarker progression in the pathogenesis of AD has been suggested, beginning with the deposition of amyloid-β (Aβ) and followed by increases in neurofibrillary tangles, synaptic loss, hippocampal atrophy, and lastly, cognitive impairment.
  
  
  OBJECTIVE
  We explored the effect of several risk factors for AD on the pattern of AD biomarker expression in normal subjects.
  
  
  METHODS
  AD biomarker evidence was examined at baseline in 96 cognitively normal elderly subjects with none or at least one of the following: ApoE4+ allele, a maternal history of AD (mFHx), sleep-disordered breathing (SDB), and longitudinal evidence of decline to mild cognitive impairment or AD (decliners) at follow-up.
  
  
  RESULTS
  Decliners and ApoE4+ subjects presented with expected reduced cerebrospinal fluid Aβ42, elevated P-tau and T-tau. In addition, decliners had fluorodeoxyglucose positron emission tomography hypometabolism in the medial temporal lobe. Individuals with mFHx demonstrated no Aβ42 effect, but had elevations in P-tau and T-tau. SDB was found to be associated with elevated Aβ42, P-tau and T-tau, as well as with reduced medial temporal lobe glucose metabolic rates.
  
  
  CONCLUSIONS
  Our results indicate a heterogeneous biomarker expression, suggesting diversity of AD pathways in at-risk presymptomatic subjects.
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, N.Y., USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Osorio
authors.forename: E
authors.initials: E
authors.lastname: Pirraglia
authors.forename: T
authors.initials: T
authors.lastname: Gumb
authors.forename: J
authors.initials: J
authors.lastname: Mantua
authors.forename: I
authors.initials: I
authors.lastname: Ayappa
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: L
authors.initials: L
authors.lastname: Mosconi
authors.forename: L
authors.initials: L
authors.lastname: Glodzik
authors.forename: M J
authors.initials: MJ
authors.lastname: de Leon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins